2000年 · 第113卷第07期

Objective To evaluate dobutamine technetium-99m methoxy isobutyl nitrile(sestamibi)single-photon emission computed tomography(Dobu-ECT)in detecting residual ischemia and identifying coronary vessel disease after myocardial infarction. Methods Sixty-two patients with confirmed myocardial infarction were studied with Dobu-ECT at the time of coronary artery angiography. Dobutamine was administered intravenously in incremental rates from 5 to 40 μg · kg-1 · min-1 at 3-minute intervals. At the highest infusion rate, 7.4 × 108 Bq 99mTc-MIBI was injected intravenously, and tomographic imaging was performed after one hour. Resting images were taken after 24 hours, with a second dose of 99m Tc-MIBI. Results The sensitivity of Dobu-ECT in detecting residual ischemia of myocardial infarction was 76%, which was higher than dobutamine electrocardiography(Dobu-ECG). Regardless of the single-, double-or triple-vessel diseases, Dobu-ECT was superior to Dobu-ECG in identifying residual ischemia(56% vs 4%, 86% vs 27%, 100% vs 47%, P < 0.01, respectively). The incidence of residual ischemia in patients receiving thrombolytic therapy was 67%, lower than patients without thrombolysis(72%)or those with an old myocardial infarction(94%). But the differences were not statistically significant. Dobu-ECT detected only 56% of ischemias in non-infarct related myocardium. Eighty-two percent of all significantly stenosed vessels were detected with Dobu-ECT, and 84% of patients with multivessel disease could be accurately identified. The sensitivity of Dobu-ECT was significantly greater for detecting severe stenosis over moderate stenosis. The sensitivity for detecting stenosis in the right coronary artery was greater than left anterior descending or left circumflex, but its specificity was lower. Conclusion Dobu-ECT can identify residual ischemia, as well as its location and extent after myocardial infarction. Dobu-ECT can also accurately detect significantly stenosed vessels. Chin Med J 2000; 113(7): 579-583

Objective To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes. Methods Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats(SHRs)left ventricular myocytes using the whole-cell configuration of patch-clamp technique, with normal Wistar rats ventricular myocytes as controls. We observed depolarizing currents(sodium current, INa; L-type calcium current, L-ICa)and repolarizing currents(inward rectifier potassium current, IK1; delayed rectifier potassium current, IK; transient outward potassium current, ItO)and compared the differences between normal and hypertrophied myocytes. Results The heart to body weight ratio of Wistar rats and SHRs was 3.70±0.29 mg/g and 5.66±0.46 mg/g, respectively(P< 0.001), and the mean cell membrane capacitances were 189.94±56.59 pF and 280.68±67.98 pF, respectively(P< 0.05). These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes. The amplitude of L-Ica of SHRs(1944±466.8 pA)was significantly greater than that of Wistar rats(1136±383.3 pA)(P< 0.001), and the current density was 6.93±1.71 pA/pF and 6.19±2.85 pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged(56.01± 13.36 ms vs 43.63±17.89 ms, P< 0.001). The amplitude of INa of SHRs(6132.5±1162.9 pA)was significantly greater than that of Wistar rats(3613.9± 794.44 pA)(P< 0.001), but there was no difference when normalized to cell capacitance(24.61±6.72 pA/pF vs 24.95±6.99 pA/pF). Channel activation and inactivation time constants were also the same. The amplitude of IK of SHRs(3461.5±1967.10 pA)was greater than that of Wistar rats(2302.4±893.72 pA)(P < 0.05), but there was no difference when normalized to cell capacitance(12.38±5.46 pA/pF vs 11.86±3.59 pA/pF). The inward portion of IK1 of SHRs was significantly lower than that of Wistar rats(11.3±2.26 pA/pF vs 14.3±3.00 pA/pF, P< 0.05), but there was no difference in the outward portion(2.360±0.86 pA/pF vs 2.957±1.27 pA/pF). The current density of Ito of SHRs(8.21± 6.64 pA/pF)was significantly lower than that of Wistar rats(19.16±6.17 pA/pF)(P< 0.001), but channel kinetics were similar, suggesting that the reduction of Ito may result from the decrease in channel number. Conclusions Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1. there was an increase of L-Ica, INa and Ik, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2. Ito was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge. The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of Ito may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity. Therefore, the reduction of Ito in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling. Chin Med J 2000; 113(7): 584-587

Objective To study whether the diacylglycerol(Dia)signaling pathway is stimulated by advanced glycosylation end products(AGEP)and to test the effect of vitamin E and aminoguanidine(AG)on the elevation of Dia induced by AGEP in cultured human umbilical vein endothelial cells(HUVECs). Methods The effects of AGEP on Dia levels in cultured HUVEC were studied with radio-enzymatic assay. Quantitative measurements of 32P phosphatidic acid were achieved by thin-layer chromatography and autoradiography. Results The Dia levels in HUVECs were increased by AGEP modified bovine serum albumin(AGEP-BSA)in a dose-dependent, biphasic manner. The early phase was rapid and transient, peaking at 15 s; the late phase reached the maximal level at 10 min and then decayed slowly. Dia levels in HUVEC exposed to different concentrations(50, 100 and 200 mg/L)of AGEP-BSA(341±14, 678±16, and 873±18 pmol/L, respectively vs control 225±10 pmol/L)and AGEP-BSA samples with various glycosylation times(4, 8 and 12 weeks)were significantly increased(270±12, 394±16, and 556±19 pmol/L)as compared with the controls. 50 and 100 mmol/L of vitamin E can reduce AGEP-BSA-induced Dia levels from 873±18 pmol/L to 764±29 and 441±21 pmol/L in HUVEC, respectively. In AG-treated(100 mmol/L)groups, the same concentration(100 and 200 mg/L)of AGEP-BSA-induced elevation of Dia was decreased to 312±8 and 351±13 pmol/L, respectively. Glycosylated low-density lipoprotein(LDL)did not affect Dia levels. Conclusion AGEP causes a robust stimulation of the Dia/protein kinase C pathway in HUVEC. Vitamin E can attenuate the AGEP-BSA-induced elevation of Dia levels. AG can suppress the ability of AGEP-BSA to increase Dia levels in HUVEC. China Med J 2000; 113(7):588-591

Objective To assess the characteristics of autonomic control of heart rate in postmenopausal women before and after hormone replacement therapy(HRT). Methods Time domain and spectral domain heart rate variability(HRV)were performed in 58 postmenopausal women before and after HRT. Results Compared with examinations at baseline, values of all HRV measurements in subjects given HRT were increased at the fourth month(P< 0.05), while they remained unchanged in the control group(P> 0.05). Results showed an inverse correlation between all measures of HRV and mean R-R interval in the treatment group. Conclusion HRT reduces sympathetic drive in postmenopausal symptomatic women. HRV may be an index of imbalance of autonomic control in perimenopausal women. Chin Med J 2000; 113(7): 592-594

Objective To evaluate the role of endogenous ouabain(E)in the development of hypertension and the characteristics of EO secretion in 1k1c(one kidney, one clipped)hypertensive rats. Methods EO content of serum and tissues in 1k1c hypertensive rats and normal control Sprague-Dawley(SD)rats was detected by the method of enzyme linked immunosorbent assay(ELISA). The relationship between serum or tissue ouabain and blood pressure was analyzed in 1 k1 c hypertensive rats. Results The ouabain content of serum, heart, kidney, adrenal gland, pituitary and hypothalamus was significantly higher in 1k1c hypertensive rats than that in normal control SD rats(2.25,2.63, 3.35, 40.37, 3.34, 15.7 μg/kg tissue in 1k1c hypertensive rats vs 1.12, 1.79, 1.73, 27.54, 1.83, 10.10 μg/kg tissue in control SD rats, respectively. P< 0.05 for all of these comparisons).The ouabain content of the adrenal gland and the hypothalamus was higher than that of other tissues or serum, both in 1 k1c rats and in control SD rats. The EO content of serum, kidney and hypothalamus was significantly correlated with blood pressure in 1k1c hypertensive rats(r= 0.59, 0.63, 0.52, respectively. P< 0.05). The ouabain content of heart, liver, adrenal gland and pituitary was not correlated with blood pressure. Conclusions EO might play an important role in the development of hypertension in 1k1c hypertensive rats. The adrenal gland may be a major source of EO and the hypothalamus-pituitary-adrenal axis may be involved in the regulation of EO secretion. Chin Med J 2000; 113(7):595-598

Objective To investigate effect of emodin on hepatic fibrosis in rats. Methods The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCI4(twice a week for 6 weeks)dissolved in olive oil. The emodin-treated rats were treated with low-dose, mediate-dose and high-dose emodin(20, 40 and 80 mg/kg body weight, once a day for 42 days)dissolved in 0.5%sodium carboxymethylcellulose(CMC), except receiving CCI4. Control group received only oliwe oil and 0.5% CMC. Liver functions were determined by standard procedure. Serum hyaluronic acid and laminin were determined by radioimmunoassay. Liver hydroxyprolines were determined. Histopathological changes were examined by optical microscopy. Results Compared with model group, the emodin-treated rats showed(1)liver functions were improved, alanine transaminase(ALT)and alkaline phosphatase(AKP)were obviously reduced, and total protein(TP)and albumin(ALB)were significantly increased;(2)serum hyaluronic acid and laminin were markedly reduced;(3)liver hydroxyproline was significantly decreased;(4)the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant(P< 0.05 or P< 0.01). Conclusion Emodin has effect on hepatic fibrosis in rats.The hepatoprotective of emodin may be one of mechanisms for liver fibrosis. Chin Med J 2000; 113(7): 599-601

Objective To study the mechanism of hepatitis C virus(HCV)replication and to test gene therapy for hepatitis C, a human liver cell line expressed HCV RNA polymerase has been established. Methods NS5B gene has been transfected into Huh-7 cells by lipofectamine. The results of transfection were confirmed by PCR and Southern blot analysis, and the level of the non-structural protein 5B(NS5B)in Huh-7 cells was detected by Western blot analysis. Results There were NS5B gene fragments and the expression of NS5B protein in Huh-7c cells transfected with pTeT-NS5B or pcDNA-NS5B plasmid. Conclusions We have established a HCV RNA polymerase expression system in Huh-7 cells which can be further used to analyze the mechanism of HCV replication and provide a cell model for gene therapy in vitro. Chin Med J 2000; 113(7): 602-605

Objective To explore the influence of reactive oxygen species(ROS)during heat shock on the activity of superoxide dismutase(SOD)and the endurance of cardiomyocytes against hypoxia-reoxygenation damage. Methods Cultured rat neonatal cardiomyocytes were divided into 5 groups(n = 6/group): normal control, anoxic control, heat shock, heat shock + SOD(150 U/ml)and exogenous ROS pretreated. Myocytes were first incubated in a C02 incubator(37℃)with Hank's solution for 30 min, followed by specific pretreatment. Heat shock was performed by incubating the cells in a 43℃ incubator for 30 min; exogenous ROS were generated by the reaction of xanthine oxidase with xanthine. After the dishes were returned to normal incubation conditions for 24 h, myocytes underwent hypoxia(3 h)and reoxygenation(1 h). Results Compared with control groups, ROS production increased after the cells experienced heat shock(1.28±0.34 nmol/mg ·protein vs 0.80±0.23 nmol/mg· protein and 0.74±0.20 nmol/mg· protein, P< 0.05)or ROS pretreatment(3.30±0.58 nmol/mg·protein, P< 0.05). 24 hours later, accompanied by attenuated cellular injury, significantly increased SOD activity was found in heat shock(2.55±0.43 U/mg· protein vs 0.77±0.12 U/mg ·protein and 0.63±0.09 U/mg ·protein, P< 0.05)and exogenous ROS pretreated(2.34±0.31 U/mg ·protein, P< 0.05)groups following reoxygenation. Moreover, opposite results were found when myocytes were treated with SOD during heat shock. Conclusions The release of ROS during heat shock triggers delayed myocardial protection by altering the activity of SOD. ROS may play an important pathophysiological role in heat shock induced myocardial protection. Chin Med J 2000; 113(7): 606-609

Objective To use non-X-ray comprehensive measurement for accurate localization of sublabio-septo-sphenoidal approach for shortening operating duration, decreasing hemorrhage, and increasing the success rate of operation. Methods Operations in 122 patients suffering from tumors in the sella turcica region used non-X-ray localizations including localization by the angle formed by the glalella, anterior nasal spina and anterior nasal spina-sella turcica; localization by the angle formed by the upper incisors, anterior nasal spina and anterior nasal spina-sella turcica; and localization by anatomical markers(determination of the midline by the nasoseptum and vomer; determination of the anterior wall of the sphenoidal sinus by the foramen of the sphenoidal sinus and vomer body; correction of the site by septum of the sphenoidal sinus; location of the center of saddle by the shape of the floor of the sella and determination of the approach direction by the damaged area in the sella turcica region)were comprehensively employed. Additionally, X-ray localization was used to correct its accuracy. Results Non-X-ray comprehensive localization was applied to 40 patients for determining the site and depth of the floor of the sella, and the preciseness of the measurement was confirmed with X-ray. Operating duration averages 2.2 hours. Non-X-ray localization was directly applied to 82 patients for comprehensively measuring the floor of the sella, and operations were successful. Operating duration averages 1.5 hours and blood transfusion averages 200 ml. No deaths and severe complications occurred. Conclusion Non-X-ray comprehensive measurement can be directly applied for precisely localizing the floor of the sella. Chin Med J 2000; 113(7): 610-612

Objective To investigate the protective effect of dl-3-n-butylphthalide(NBP)as an anti-cerebral ischemic drug on brain damage 24 h after closed head injury in mice. Methods Closed head injury was induced by dropping a 50-g weight from a height of 18 cm on a metal impounder resting on the parietal bone in mice. Results The neurotraumatic model induced impairment of memory function, significant cerebral edema, and disruption of the blood-brain barrier. dl-3-n-butylphthalide(50 mg · kg-1)given intraperitoneally 5 minutes and 60 minutes after the onset of closed head injury was found to attenuate the impairment of memory function(P< 0.05), alleviate brain edema in the injured cerebral cortex(P< 0.05), and reduce extravasation of plasma protein bound to Evans blue dye by 63.5%(P< 0.01). NBP was also shown to increase the activity of choline acetyltransferase in the injured cortex to 0.83±0.21 ng·min-1 · mg-1(P< 0.01, compared with 0.48±0.14 ng· min-1 · mg-1 of vehicle group). Conclusion NBP provides therapeutic response in experimental closed head injury. Chin Med J 2000; 113(7): 613-616